Randomized clinical trials, a large NCI-Kaiser Permanente real-world follow-up study involving over one million women, and the three US FDA registration trials clearly demonstrate that HPV primary screening for cervical cancer is safe and effective. Co-testing that combines both HPV testing and cytology offers minimal, if any, additional benefit over HPV primary testing and increases costs, requires follow-up of HPV-negative women with ASCUS and LSIL that can lead to unnecessary colposcopies/biopsies and retains the medico-legal risk of false-negative cytology results. A number of countries have adopted HPV primary screening for their national screening programs and in the United States HPV primary screening is now classified as the preferred screening approach for women >25 years by the 2020 American Cancer Society guidelines.

Cervical cancer, with a global incidence of 570,000 annually, causes 7.5% of all female cancer deaths. Screening has prevented about 80% of cases in developed countries. Evidence however continues to evolve on the best modality of screening. Primary screening with high-risk human papilloma virus (Hr-HPV) alone will lead to unnecessary interventions among women <30 years in whom Hr-HPV is very common but always transient. Based on this, the WHO, ACOG and United States Preventative Task Force do not recommend screening women <30 years with Hr-HPV. In addition, the American Society for Clinical Pathology advised that women undergoing Hr-HPV testing should have cytological examination at some point during their screening, as 9–10% of invasive cancers and 8.3–14% of high-grade squamous intraepithelial lesion (HSIL) are Hr-HPV negative, and Hr-HPV screening may cause delayed diagnosis and higher stage tumors. As countries transition to Hr-HPV-based screening, it is important to acknowledge the limitations and refine the utilization of the test.

The role of surgical cytoreduction in the management of primary ovarian cancer is well established. Unfortunately, the majority of patients develop recurrent disease. In the recurrent setting, the clinical benefit of surgical cytoreduction is debatable. The goal of treatment of recurrent ovarian cancer is to prolong remission, improve quality of life, and improve survival.

The recommended treatment of endometrial cancer is total hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. Fertility-sparing options are supported only by retrospective data. Complete durable responses to continuous progestins for fertility-sparing are only 50%, with recurrence rates of 35%. Moreover, there is recent evidence that fertility-sparing treatment negatively affects progression-free survival. These substantial risks must be weighed against the modest live birth rates of approximately 28% with 81% of live births requiring the assistance of reproductive technology. Ovarian preservation after hysterectomy is another option, however the risk of synchronous ovarian cancer may be higher in young women, and the opportunity to diagnose familial cancer syndromes may be missed. Further prospective and long-term studies must be performed to assess oncologic outcomes associated with fertility-sparing treatment in early-stage endometrial cancer before this option can be deemed safe.

Cervical carcinomas (CC) arise in large part due to infection with human papillomaviruses (HPV), with persistence of viral oncogenic proteins E6 and E7 in most if not all CC. These proteins serve as a source of “foreign” antigens, generating a strong rationale for immunotherapeutic approaches. A number of approaches including cancer vaccines, adoptive cell therapy, and immune checkpoint blockade have been explored in cervical cancer and in pre-cancerous lesions, each demonstrating an ability to induce deep and durable responses, though benefits have been limited to a minority of patients to date. Herein we summarize the results of these studies, discuss ongoing combination trials, and provide perspectives for future of immunotherapy in cervical cancer.

Two prospective randomized controlled trials and several retrospective studies have investigated the benefit of Heated Intraperitoneal Chemotherapy (HIPEC) in the primary management of ovarian cancer. The results of the prospective trials are discordant. Additionally, data from a recent systematic review failed to show a beneficial effect of HIPEC. Therefore, currently there is no role for HIPEC in the first-line therapy of ovarian cancer.

Ovarian cancer consistently remains the most lethal gynecologic malignancy because it is predominantly found at an advanced stage. Often, despite efforts to ascertain the potential for successful surgical resection based on imaging, clinical symptomatology, and serum CA-125, it is frequently not determined until the time of surgery with widespread metastasis throughout the peritoneal cavity that was not seen on standard axial imaging. Secondary to the possibility of this “ineffective” or “unnecessary” laparotomy only to discover unresectable cancer, the implementation of diagnostic laparoscopy to determine the extent of the disease and the ability to perform a complete cytoreductive surgery has been adapted by some surgeons. Though data is varied as to the effectiveness of laparoscopy to determine the resectability of advanced ovarian cancer, it adds another layer of diagnostic information through a minimally invasive modality and ultimately prevents patients who are deemed unresectable from going through an invasive, painful procedure that often requires at least a single-day postoperative hospitalization and could delay the initiation of neoadjuvant chemotherapy if there are postoperative complications.

The standard treatment in patients with stage IB3–IIB cervical cancer is concomitant chemoradiation (CTRT). Neoadjuvant chemotherapy followed by surgery (NACT-surgery), recently reported in comparison with CTRT in two phase III randomized trials, has been proposed as an alternative treatment in these patients. The two studies were similarly designed with a few differences. Their results, in aggregate, show that disease-free survival (DFS) is significantly superior with CTRT compared to NACT-surgery while overall survival (OS) is not significantly different with these two treatments. In the NACT-surgery arms of TMH and EORTC studies, 28% and 24% patients could not undergo surgery, respectively, and 44.6% and 27% patients received radiotherapy, respectively. Although the benefit of CTRT seemed to be concentrated in patients with stage IIB, there is no suggestion that NACT-surgery results in better outcome in any stage. Therefore, CTRT should be the standard of care in patients with locally advanced cervical cancer.

Re-excision is the best treatment for stage I vulvar squamous cell carcinoma with close or positive surgical margins. Given the relative rarity of stage I vulvar cancer, to date there are no prospective studies that directly evaluate re-excision versus adjuvant radiation for close or positive margins. More recent retrospective studies question if margin status truly predicts recurrence and if any further treatment following primary excision is warranted. Vulvar surveillance is simple with direct visualization, and re-excision is effective for most recurrences. Adjuvant radiation has a host of morbid and often permanent side effects with nearly all patients experiencing some degree of these complications. Further, adjuvant radiation complicates treatment of future recurrences by hampering future healing and eliminating radiation as a future treatment option. Thus, although adjuvant vulvar radiation may have the potential to reduce local recurrence, the associated long-term morbidity risk far outweighs the benefits, and re-excision in the treatment of choice for patients with stage I vulvar squamous cell carcinoma with close or positive surgical margins.

High-risk endometrial cancer represents a heterogenous group of patients, including nonendometroid tumor types such as serous carcinoma, that are characterized by poorer overall survival, most likely due to higher rates of distant metastasis. For this reason, adjuvant chemotherapy can be considered in this particular population.Unfortunately, as these tumors represent an infrequent subset of patients, data are very limited.

A subgroup analysis of the NSGO9501/EORTC 55991 and MaNGO-ILIADE III trials did not show a survival benefit for patients with serous or clear-cell tumors. Data from retrospective analysis suggest that, in patients who did not undergo complete surgical staging, adjuvant therapy was associated with greater oncological outcomes.

In conclusion, adjuvant therapy should be considered in non-staged patients, when complete surgical staging is not feasible or within clinical trials. Future prospective clinical trials, including the constantly evolving molecular categorization, are needed to explore more effective treatment strategy for this unique patient population.

The fimbriated end of the fallopian tube plays a pivotal role in the pathogenesis of pelvic high-grade serous carcinomas (HGSC). While risk-reducing salpingo-oohprectomy (RRSO) is the standard of care for patients with genetic risk for developing HGSC, the detrimental effects of premature menopause on both health and quality of life are unacceptable to many patients. Risk-reducing early salpingectomy with delayed oophorectomy (RRESDO) has the potential to offer risk-reduction, without the toxicity of premature menopause and infertility. An individualized “previvorship” plan incorporating this option allows for patient-centered planning, with the potential for enhanced quality of life, earlier detection of precursor lesions, and possibly a greater impact in risk-reduction.

The concept that aggressive cytoreduction attempts be made for all surgical candidates does not seem to be a realistic goal as evidenced by recent publications. There is no doubt that primary surgery has an important role, but equally so does neo-adjuvant chemotherapy. The latter approach is evidence based, showing similar survival patterns but less morbidities and postsurgical in-patient stay. However, randomized trials where the evidence is contrary to accepted practise often generate heated criticisms, others fitting beliefs are applauded. It is welcome that there is an ongoing trial addressing primary surgery, and hopefully this will contribute in identifying those where aggressive primary surgery is best employed. The survival for advanced ovarian cancer remains poor, and rather than considering a single approach as optimum, strategies to individualize treatments and examine novel therapeutic approaches seems a more logical way to improve survival rates.

Rising CA-125 levels can detect relapsed ovarian cancer about six months before symptoms develop. Therefore, many asymptomatic patients have routine CA-125 measurements during follow-up. The only trial of CA-125 surveillance after first-line therapy randomized patients to early or delayed treatment after a doubling of CA-125 level. It showed those in the early arm had no survival benefit and worse quality of life. The trial was criticized as few patients had secondary surgery, yet randomized trials show conflicting results on the value surgery. Patients should be aware that recurrent ovarian cancer is not curable and require information on surveillance options.

The extent of residual disease following upfront cytoreductive surgery for stage III–IV ovarian cancer is one of the strongest prognostic factors for progression-free and overall survival. Currently, there are two approaches proposed in order to achieve minimal residual disease: primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT)) followed by interval debulking surgery. In the last decade, the field has developed a greater understanding of both approaches and more importantly, several prospective randomized trials were designed to address the question of which patients are most or least likely to benefit from primary debulking surgery versus neoadjuvant chemotherapy.

Among patients diagnosed with stage I granulosa cell tumors (GCTs) of the ovary, 25% will experience recurrent disease, after a median of four to six years from initial diagnosis [1]. GCTs are rare tumors and have a slow, indolent course, with recurrences registered even after several decades from initial diagnosis [2].

Both the National Comprehensive Cancer Network (NCCN) and the Society for Gynecologic Oncology (SGO) support the use of sentinel lymph node biopsy (SLNB) in the staging of apparent uterine-confined endometrial cancer. However, these recommendations are largely informed by retrospective and limited prospective studies performed in women with low-grade endometrial cancer (LGEC). The use of SLNB in women with high-grade endometrial cancers (HGEC), which are more biologically aggressive, have a higher risk of lymphatic spread, and poorer survival outcomes than those with LGEC, remains a matter of debate.

Endometrial cancer remains the most common gynecologic malignancy diagnosed in the United States. Although most patients present with low-grade and early-stage disease, risk of endometrial cancer recurrence ranges from 8–64%, depending mostly on tumor-specific prognostic factors. Appropriate treatment options vary depending on extent of recurrent disease, previous therapies used, and intent of treatment, curative versus palliative. Randomized data to inform on outcomes of cytoreductive surgery in the treatment of recurrent endometrial cancer are non-existent. Given the limitations of the available evidence, as well as the emergence of better systemic therapeutic approaches, secondary cytoreduction in the management of patients with recurrent endometrial cancer is not recommended.

Changes in serum CA-125 levels predict response to chemotherapy and survival in women with advanced epithelial ovarian cancer. Although often used to monitor for recurrence, randomized trial data do not suggest that treatment based on a rising CA-125 alone impacts prognosis if secondary cytoreduction is not under consideration. CA-125 surveillance may still provide benefits to patients who are likely to achieve a complete resection at secondary cytoreduction – assuming that early identification of recurrent disease based on a rising CA-125 level leads to a higher chance of complete gross resection. CA-125 surveillance also provides patients with useful information about prognosis and impending recurrence – regardless of whether this information impacts survival directly. As such, the routine use of CA-125 surveillance should be considered as an individualized option for patients based on disease characteristics and personal preferences.

Malignant bowel obstruction is one of the toughest clinical challenges in gynecology. Few rigorous clinical trials exist to guide management.While conservative options should be exhausted first, palliative bowel surgery remains the only approach offering the possibility of quality time, restoration of oral nutrition, and on-going cancer-directed therapy. The capacity to address malignant bowel obstruction becomes ever more critical as many of the most promising new treatments for gynecologic malignancy are targeted biologic oral agents. The best candidates for surgery are obstructed in a single location, naive to prior bowel obstruction surgery, have treatment options remaining, and have minimal ascites or carcinomatosis. Postoperative 30-day mortality after palliative bowel surgery ranges from 4–40% and perioperative morbidity including postoperative pain, bowel leaks, abscess, sepsis are high, range from 5–86%.Thus, the choice to proceed with surgery requires exceptional doctor–patient communication, a highly skilled surgical team, and meticulous patient selection.

The management of patients with platinum-resistant recurrent epithelial ovarian cancer (EOC) poses a significant challenge. Traditionally treatment has involved the use of non-platinum chemotherapeutic agents, including PEGylated liposomal doxorubicin (PLD), topotecan, gemcitabine, and paclitaxel, used as monotherapy with response rates of 10–15%, progression-free survival (PFS) of three to four months and overall survival (OS) of approximately 12 months [1]. These agents have had limited efficacy and failed to demonstrate a meaningful OS benefit at the risk of chemotherapy toxicity. Through advancements in integrated genomic analysis, an increased understanding of the underlying molecular characteristics of EOC has led to the development of various molecularly targeted strategies designed to advance the field beyond single agent chemotherapy.